Physical morbidity and mortality disparities consistently favor non-Hispanic whites over black Americans. Epidemiological studies reveal that black Americans suffer the same or lower rates of mental disorders as whites. In highly stressful environments individuals often engage in negative health behaviors, e.g. smoking, alcohol use and abuse, drug use, and over-eating, to cope with the stressors of daily life. These behaviors, perhaps through mechanisms associated with the HPA axis, alleviate the stressful reactions to these environmental exposures;the same chronic stress exposures and poor health behaviors that are silently affecting biological pathways to eventual negative physical health morbidity and mortality. Thus, lower rates of mental disorders among the African American population are at the expense of higher physical health morbidities and mortality in comparison to the non-Hispanic white population. We hypothesize and present a complex framework involving environmental factors, chronic stressors, and the stress response through the HPA-Axis, that account for the interrelationship among mental disorders and cardiovascular health outcomes. The observed epidemiological and clinical physical health/mental disorder paradox will be addressed using: 1) analyses of existing large epidemiological datasets;2) analyses of survey and clinical datasets containing epidemiological, risk factor, and biological indicators;and, 3) a longitudinal cohort, clinical study examining in detail the relationship among biological and social risk factors, biomarkers for cardiovascular health and mood disorders, among black and white women. There are three interrelated, multi-disciplinary, specific aims, at increasing levels of specificity: 1) analyses of observational/epidemiological data on physical and mental disorders, 2) analyses of potential biological pathways of physical morbidity and mental disorder interrelationships in observational/epidemiological studies, and 3) a clinic based 112 month longitudinal study of potential interventions that affect cardiovascular risk behaviors and risk and resilience biomarkers, and risks for mood disorders and biomarkers for stress and HPA functioning, among African American as compared to non-Hispanic white women.